Variant chr8-8797398-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004225.3(MFHAS1):c.3092C>T(p.Pro1031Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MFHAS1
NM_004225.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.28

Variant links:

Genes affected

MFHAS1 (HGNC:16982): (multifunctional ROCO family signaling regulator 1) Identified in a human 8p amplicon, this gene is a potential oncogene whose expression is enhanced in some malignant fibrous histiocytomas (MFH). The primary structure of its product includes an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, which are structural or functional elements for interactions among proteins related to the cell cycle, and which suggest that overexpression might be oncogenic with respect to MFH. [provided by RefSeq, Jul 2008]

MFHAS1 links:

MFHAS1 (HGNC:):

MFHAS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFHAS1	NM_004225.3 linkuse as main transcript	c.3092C>T	p.Pro1031Leu	missense_variant	2/3	ENST00000276282.7	NP_004216.2	Q9Y4C4
MFHAS1	XM_047422419.1 linkuse as main transcript	c.3092C>T	p.Pro1031Leu	missense_variant	2/3		XP_047278375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MFHAS1	ENST00000276282.7 linkuse as main transcript	c.3092C>T	p.Pro1031Leu	missense_variant	2/3	1	NM_004225.3	ENSP00000276282.6	Q9Y4C4
MFHAS1	ENST00000520091.1 linkuse as main transcript	n.410C>T		non_coding_transcript_exon_variant	2/4	4
MFHAS1	ENST00000520715.5 linkuse as main transcript	n.139C>T		non_coding_transcript_exon_variant	2/3	3
MFHAS1	ENST00000521881.5 linkuse as main transcript	n.136C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.3092C>T (p.P1031L) alteration is located in exon 2 (coding exon 2) of the MFHAS1 gene. This alteration results from a C to T substitution at nucleotide position 3092, causing the proline (P) at amino acid position 1031 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.59

Sift

Benign

0.034

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.59

MutPred

0.49

Loss of disorder (P = 0.0073);

MVP

0.85

MPC

0.79

ClinPred

0.99

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over